Cyanocobalamin is a vitamin B.sub.12, and is one of the B.sub.12 class of vitamins which includes vitamin B.sub.12a (hydroxocobalamin), vitamin B.sub.12b (aquacobalamin), vitamin B.sub.12c (nitrilocobalamin), coenzyme B.sub.12 (5'Odeoxyadenosine cobalamine) and methyl B.sub.12 (methyl cobalamine). Cyanocobalamin is the principal member of the class, and the most widely employed in medicine. This invention will be described as it relates to cyanocobalamin, but those skilled in the art will recognize that the invention is aplicable to the class.
Vitamin B.sub.12 is an essential compound for normal growth, hematopoiesis, production of all epithelial cells and maintenance of myelin throughout the nervous system. It was first isolated from liver concentrate by Rickes and his coworkers in 1948 and structurally elucidated by Hodgkin and her coworkers in the late 1950's. It is currently commercially available as a tablet and as an injectable.
Therapeutically, vitamin B.sub.12 is employed in the treatment of a variety of B.sub.12 deficiency afflictions, principally anemias such as pernicious and diplyllobothrium latum. Although the minimum daily requirement of vitamin B.sub.12 is approximately 0.1 .mu.g, the generally prescribed initial therapeutic dose is 100 to 1000 .mu.g given intramuscularly. Maintenance therapy with vitamin B.sub.12 is usually 100 .mu.g intramuscularly, monthly and must be continued for life.
Since pernicious anemia is often a disease of later years when many sufferers have reduced muscle mass or are atrophic, repeated intramuscular injections of vitamin B.sub.12 can be inconvenient, painful and often require doctor's visits. In some cases at least in the early stages, hospitalization is required. As a result, there is a need for a more convenient, less painful and less expensive method of administering vitamin B.sub.12, particularly one that would not require hospitalization or repeated physician contacts.
Unfortunately, up to the present time no efficient method of administering B.sub.12 which will achieve therapeutically useful blood levels of the vitamin except parenteral administration has been devised.
In 1953 and 1954 Monto et al in Am. J. Med. Sci., 223, 113 (1953) and Arch. of Int. Med. 93,219 (1954) described administration of B.sub.12 by nasal inhalation and instillation. The vehicles for administration were aqueous isotonic sodium chloride solution and lactose powder. Although the results were reported as effective, safe and economical, the fact is that parenteral administration remains the only method regarded by the medical community as a safe, reliable and effective method for treating vitamin B.sub.12 deficiencies in humans. No composition for nasal inhalation or instillation has become commercially available for nasal administration to mammals. Neither have there been any further publications describing nasal inhalation or instillation of which applicant is aware.
The difficulty with nasal instillation by nasal dosage as the procedure is described in the cited articles is that most of the B.sub.12 passes immediately into the throat. It is not in contact with the nasal mucosa for a sufficient period of time to permit useful and uniform absorption. Most of the B.sub.12 so administered is, in fact wasted.
Compositions have now been discovered for the nasal administration of B.sub.12 which can be kept in contact with the nasal mucosa for an extended period of time. During the time the compositions are in such contact, the B.sub.12 is uniformly absorbed from the compositions through the nasal mucosa and is then uniformly distributed systemically. The use of the compositions, because of the efficiency with which the B.sub.12 is absorbed allows the use much lesser amounts of B.sub.12 than is normally present in parenteral B.sub.12 compositions. Moreover, since the patient can self administer the B.sub.12, the need for hospitalization or physician contacts is minimized and may even be eliminated.